This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is investigating the protein-protein interactions between the Alzheimer's peptide A-beta and other prtoeins, such as alpha-B crystallin, which may mediate neurotoxicity in Alzheimer's disease, and with metals. Western blots have provided some evidence for colocalization of A-beta and alpha-B-crystallin in AD deposits. Preliminary evidence indicates that alpha-B crystallin blocks A-beta fibril formation and potentiates the neurotoxicity of recombinant human A-beta 1-42. Experiments are now underway to identify Ab-aB crystallin crosslink signature(s) in vitro using purified proteins and mass spectrometry. If this proves successful, later experiments will explore the occurrence of such crosslinks in human tissue samples. Recent experiments have begun to use 2D-MALDI-TOF MS/MS to explore the spatial distribution of proteins in mouse brain which has already been analyzed by ICP-MS to locate metal distributions.